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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction显示文摘AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFLD) with or without progressive fibrosis: Lep^(ob)/Lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMLN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESULTS When challenged with AMLN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMLN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMLN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMLN mice compared to FATZO AMLN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 BL6 J control mice, but significantly perturbed in ob/ob mice. CONCLUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is a key factor for development of hepatic injury and fibrosis in these mouse models. | Michelle L Boland Stephanie Oldham Brandon B Boland Sarah Will Jean-Martin Lapointe Silvia Guionaud Christopher J Rhodes James L Trevaskis | 2018 | World Journal of Gastroenterology2018，24，16： | 7 |
| 3 | Meeting report:a hard look at the state of enamel research显示文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines(ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research(NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3 D cell culture/organoids. Scientists from a number of disciplines,representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field. | ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer | 2017 | International Journal of Oral Science2017，9，4： | 3 |
| 4 | IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis显示文摘AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association. | Sarah Fischer Erzsébet Kovesdi Lili Magyari Veronika Csongei Kinga Hadzsiev Béla Melegh Péter Hegyi Patrícia Sarlós | 2017 | World Journal of Gastroenterology2017，23，3： | 3 |
| 5 | Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/Ipr mouse model of systemic lupus erythematosus显示文摘热吃惊蛋白质 90 的提高的表示(HSP90 ) 在全身的豺狼座 erythematosus (SLE ) 的肾和浆液被发现了病人和 MRL/Mp-Fas lpr /Fas lpr (MRL/lpr ) 自体免疫的老鼠。如果 HSP90 的抑制将在 MRL/lpr 老鼠减少疾病,我们调查了。在在 vivo 的 vitro,有在 IL-6 的有免疫力刺激的显示出的减少的表示以前的 HSP90 禁止者 Geldanamycin 的 mesangial 房间的预告的处理, IL-12 和号码,我们发现当与 C57BL/6 相比鼠标和 MRL/lpr 鼠标与 HSP90 禁止者 17-DMAG 对待时, HSP90 表示在 MRL/lpr 肾被提高。与 17-DMAG 对待的 MRL/lpr 老鼠显示出减少的 proteinuria 并且减少了浆液 anti-dsDNA 抗体生产。Glomerulonephritis 和 glomerular IgG 和 C3 没被 17-DMAG 的管理显著地在 MRL/lpr 影响。17-DMAG 增加了 CD8 + T 房间,减少的双 negative T 房间,减少 CD4/CD8 比率和减少的小囊的 B 房间。这些研究建议 HSP90 可以在调整 T 房间区别和激活起一个作用并且 HSP90 抑制可以在豺狼座减少发炎。 | Samuel K Shimp III Cristen B Chafin Nicole L Regna Sarah E Hammond Molly A Read David L Caudell Marissa Nichole Rylander Christopher M Reilly | 2012 | Cellular & Molecular Immunology2012，9，3： | 3 |
| 6 | Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer显示文摘Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa. | Andreas Marx Lena Koopmann Doris Hoflmayer Franziska Büscheck Claudia Hube-Magg Stefan Steurer Till Eichenauer Till S.Clauditz Waldemar Wilczak Ronald Simon Guido Sauter Jakob R.Izbicki Hartwig Huland Hans Heinzer Markus Graefen Alexander Haese Thorsten Schlomm Christian Bernreuther Patrick Lebok Sarah Bonk | 2021 | Cancer Biology & Medicine2021，18，1： | 3 |
| 7 | Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas显示文摘Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies. | Crystal S Seldon Lauren E Colbert William A Hall Sarah B Fisher David S Yu Jerome C Landry | 2016 | World Journal of Gastrointestinal Oncology2016，8，4： | 2 |
| 8 | The CELLULOSE-SYNTHASE LIKE C (CSLC) Family of Barley Includes Members that Are Integral Membrane Proteins Targeted to the Plasma Membrane显示文摘纤维素象 SYNTHASE 一样 C (CSLC ) 家庭是在被认为在苔藓和脉管的植物的分叉前产生了的 CELLULOSE SYNTHASE/CELLULOSE 象 SYNTHASE 一样(CESA/CSL ) 多糖 synthase 总科以内的一个古老的系。作为在 flowering 植物的研究, Arabidopsis 建议了合成( 1,4 )-- xyloglucan ( XyG )的 glucan 脊梁,,拴住邻近的纤维素 microfibrils 到对方的墙多糖为 CSLC 的可能的功能, CSLC 功能在大麦( Hordeum vulgare L.)被调查,有在它的墙中的 XyG 的低数量的种。四大麦 CSLC 基因被识别(指明的 HvCSLC14 ) 。种系发生的分析在 flowering 植物揭示 CSLC 的三很好支持的 clades,与有在二这些 clades 的代表的大麦。四大麦 CSLC 在各种各样的纸巾被表示,与,包括有主要、第二等的房间墙的房间在在所有房间检测抄本的 situ PCR coleoptile 和根打字。合作表示分析证明 HvCSLC3 并列地与通常认为的 XyG xylosyltransferase 基因被表示。两免疫 -- 他们和膜分别证明 HvCSLC2 位于大麦的血浆膜暂停有教养的房间并且不在象 endoplasmic 那样的内部膜蜂窝胃或 Golgi 仪器。基于我们多糖合成的亚 cellular 地点的当前的知识,我们断定 CSLC 家庭可能包含多糖 synthase 的超过一种类型。 | Fenny M. Dwivany Dina Yulia Rachel A, Burton Neil J. Shirley Sarah M. Wilson Geoffrey B, Fincher Antony Bacic Ed Newbigin Monika S. Doblin | 2009 | Molecular Plant2009，2，5： | 2 |
| 9 | Emergency department patients with small bowel obstruction: What is the anticipated clinical course?显示文摘BACKGROUND:Emergency physicians(EPs)often care for patients with acute small bowel obstruction.While some patients require exploratory laparotomy,others are managed successfully with supportive care.We aimed to determine features that predict the need for operative management in emergency department(ED)patients with small bowel obstruction(SBO).METHODS:We performed a retrospective chart review of 370 consecutive patients admitted to a large urban academic teaching hospital with a diagnosis of SBO over a two-year period.We evaluated demographic characters(prior SBO,prior abdominal surgery,active malignancy)and clinical findings(leukocytosis and lactic acid)to determine features associated with the need for urgent operative intervention.RESULTS:Patients with a prior SBO were less likely to undergo operative intervention[20.3%(42/207)]compared to those without a prior SBO[35.2%(57/162)].Abnormal bloodwork was not associated with need for operative intervention.68%of patients with CT scan findings of both an SBO and a hernia,however,were operatively managed.CONCLUSIONS:Patients with a history of SBO were less likely to require operative intervention at any point during their hospitalization.Abnormal bloodwork was not associated with operative intervention.The CT finding of a hernia,however,predicted the need for operative intervention,while other findings(ascites,duodenal thickening)did not.Further research would be helpful to construct a prediction rule,which could help community EPs determine which patients may benefit from expedited transfer for operative management,and which patients could be safely managed conservatively as an initial treatment strategy. | Sarah E Frasure Amy Hildreth Sukhjit Takhar Michael B Stone | 2016 | World Journal of Emergency Medicine2016，7，1： | 2 |
| 10 | Occurrence and Biomagnificatien of Polychlorinated Naphthaleoes and Non-and Monoortho PCBs in Lake Ontario Sediment and Biota显示文摘 | Paul A H Sarah B Gewurtz D | 2008 | Environmental Science & Technology2008，42，： | 1 |
| 11 | Disease complex in coffee involving Meliodogyne arabicida and Fusarium oxysporus 显示文摘 | BERTRAND B NUNEZ C SARAH J L | 2000 | Plant Pathology2000，49，： | 1 |
| 12 | 显示文摘 | Sarah S W Donia B Jason A S | 2003 | Chemical Engi- neering Journal2003，95，1： | 1 |
| 13 | Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus 显示文摘 | CHRISTOPHER G B SARAH F CECILIA M L | 2010 | PLoS One2010，5，14： | 1 |
| 14 | Extraction and characterisation of lipids from Antarctic krill (Euphausia superba)显示文摘 | JOSEPH C G MATTHEW P D SARAH K B | 2010 | Food Chemistry2010，125，3： | 1 |
| 15 | Tourism management de- velopment and cultural policies in China显示文摘 | Trevor H B Sofield Fung Mei Sarah Li | 1996 | Annals of Tourism Re- search1996，23，2： | 1 |
| 16 | Over-expression of sphingosinekinase-1 enhances a progenitor phenotype in humanendothelial cells显示文摘 | Barrett Jeffrey M Parham Kate A Pippal Jyotsna B CockshellMichaelia P Moretti Paul A B Brice Sarah L Pitson StuartM Bonder Claudine S | 2011 | Microcirculation2011，187，： | 1 |
| 17 | Genetic control of chicken heterophil function in advanced intercross lines:associations with novel and with known Salmonella resistance loci and a likely mechanism for cell death in extracellular trap production显示文摘 | Sarah B Chuammitri P Andreasen C B | | 0，，： | 1 |
| 18 | A new short and efficient synthetic route to C8-N-acetylarylamine 2'-deoxyguanosine phosphoramidites显示文摘 | NICOLAS B SARAH K MARCUS S | 2007 | Synthesis2007，24，： | 1 |
| 19 | Using 3He/4He isotope ratios to identify the source of deep reservoir contributions to shallow fluids and soil gas显示文摘 | Sarah J M Chris J B | 2012 | Chemical Geology2012，，： | 1 |
| 20 | Geochemical and geo-statistical assessment of selected heavy metals in the surface sedi- ments of the GorganBay, Iran显示文摘 | Kazem D B Hossein B Sarah H | 2012 | Marine Pollution Bulletin2012，64，12： | 1 |
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